Fluorine in Peptides: The Synthesis of α‐Fluoro‐β‐Amino Dipeptides by Direct Deoxofluorination/Rearrangement of N‐Seryl Dipeptides |
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Authors: | Daniel L Smith Alexandra M Z Slawin David O'Hagan |
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Institution: | EastChem School of Chemistry, University of St Andrews, North Haugh, St Andrews, KY16 9ST, UK, (phone: +44?1334?467176) |
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Abstract: | This article describes the stereo‐ and regioselectivity of the deoxofluorination of N‐terminal dipeptides bearing a serine residue to generate, after rearrangement, α‐fluoro‐β‐amine‐terminated dipeptides. The ratio of the rearranged α‐fluorinated regioisomer is increased, relative to the non‐rearranged β‐fluoro isomer, with N‐alkylated amides. Otherwise, an intramolecular H‐bond between the free amine and the amide NH suppresses formation of the key aziridinium intermediate required for α‐fluorination. N‐Methyl and N‐allyl amides give exclusively α‐fluorination products. Subsequent deprotection of the N‐allyl amide to give a α‐fluoro‐β‐amino dipeptide product is demonstrated. |
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Keywords: | Peptides Deoxofluorination/rearrangement N‐Seryl dipeptides Fluorine compounds |
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